This grant proposal outlines a five-year training program for the development of an academic career in molecular biology. The principal investigator is a fellowship-trained clinician who proposes to expand and diversify his scientific ability through intensive coursework and reentered research training. The didactic portion of this program will consist of graduate level coursework at Duke University and regular sessions with the proposed mentors, Drs Klintworth and Bowes Rickman. Dr Klintworth is director of the Ophthalmic Genetics Center at Duke University and has expertise in studying genetically determined diseases of the eye. Dr Bowes Rickman is an Assistant Professor of Ophthalmology and Cell Biology and has expertise in characterizing mRNAs and proteins in ocular disorders. The proposed research is to investigate the molecular mechanisms that are associated with the development of pseudoexfoliation syndrome (PEX) and pseudoexfoliation syndrome with glaucoma (PEX-G) using gene array technologies. PEX is an idiopathic systemic disease characterized by fibrillar deposits in multiple ocular and non-ocular tissues. PEX is the most common identifiable cause of open angle glaucoma worldwide and is phenotypically distinct from primary open angle glaucoma. Growing evidence suggests that PEX is a late onset inherited disorder. Despite the prevalence of PEX and PEX-G little is known about their underlying molecular mechanisms. In short, we propose to: 1) Identify genes or ESTs involved in the pathogenesis of PEX using gene array technologies 2) Characterize/deduce gene sequences 3) Identify differences in gene expression between PEX and PEX-G and 4) Ascertain and recruit additional PEX patients and families. These investigations are critical to understanding the molecular basis of PEX and any modifying genetic factors that would predispose to the development of glaucoma. The Ophthalmology department at Duke University is an ideal setting for training physician-scientists and has an established track record of strong support for promising clinician-scientists.